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Endothelin-1 is a potent constrictor in conductive and resistive coronary arteries
J R Tippins1, J W Antoniw, A Maseri
1Cardiovascular Research Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Insights
Endothelin-1 (ET-1) causes vasoconstriction, particularly in smaller coronary arteries. This suggests ET-1 may induce cardiac ischemia by constricting small vessels, not by epicardial spasm.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor peptide.
- The precise site of ET-1 action within the coronary vasculature remains to be fully elucidated.
Purpose of the Study:
- To investigate the site of action of endothelin-1 (ET-1) in canine and porcine coronary arteries and myocardium.
- To determine whether ET-1 mediates its effects via epicardial coronary artery spasm or constriction of smaller resistive vessels.
Main Methods:
- In vitro studies using canine and porcine coronary artery ring preparations of varying diameters.
- In vitro studies using perfused canine and porcine myocardium.
Main Results:
- ET-1 exhibited a more potent vasoconstrictor effect in smaller diameter coronary artery ring preparations.
- The EC50 (effective concentration for 50% response) for ET-1 decreased significantly with decreasing vessel diameter.
- The EC50 of ET-1 in perfused myocardium was substantially lower than in the smallest ring preparations.
Conclusions:
- ET-1's potent vasoconstriction in small coronary arteries suggests a primary role in regulating coronary blood flow.
- The findings indicate that ET-1 may induce cardiac ischemia through constriction of small resistive coronary vessels, rather than epicardial artery spasm.
Abstract:
The action of endothelin-1 (ET-1) in canine and porcine coronary artery ring preparations and perfused canine and porcine myocardium was examined in vitro to determine the site of action of ET-1 in the coronary vasculature. ET-1 had a vasoconstrictor effect that was more potent in smaller diameter ring preparations. The EC50s for both canine and porcine ring preparations decreased with a decrease in vessel diameter and the EC50 of ET-1 in the perfused myocardium was three to four times lower than in the smallest ring preparation. The results suggest that ET-1 may cause cardiac ischemia by constriction of resistive vessels rather than by epicardial coronary artery spasm.